Sphingosine kinase 1-interacting protein is a novel regulator of glucose-stimulated insulin secretion

Abstract Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) i...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Yu Wang, Shin-ichi Harashima, Yanyan Liu, Ryota Usui, Nobuya Inagaki
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2017
Materias:
R
Q
Acceso en línea:https://doaj.org/article/b1fa3fef52d4474db7a00a0becb7d055
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Abstract Glucose-stimulated insulin secretion (GSIS) is essential in keeping blood glucose levels within normal range. GSIS is impaired in type 2 diabetes, and its recovery is crucial in treatment of the disease. We find here that sphingosine kinase 1-interacting protein (SKIP, also called Sphkap) is highly expressed in pancreatic β-cells but not in α-cells. Intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP−/− mice compared to SKIP+/+ mice, but exendin-4-enhanced insulin secretion was masked. GSIS was amplified more in SKIP−/− but exendin-4-enhanced insulin secretion was masked compared to that in SKIP+/+ islets. The ATP and cAMP content were similarly increased in SKIP+/+ and SKIP−/− islets; depolarization-evoked, PKA and cAMP-mediated insulin secretion were not affected. Inhibition of PDE activity equally augmented GSIS in SKIP+/+ and SKIP−/− islets. These results indicate that SKIP modulates GSIS by a pathway distinct from that of cAMP-, PDE- and sphingosine kinase-dependent pathways.